OVERVIEW: DEVELOPMENT OF ACISR RESEARCH CAPACITY, RATIONALE, MISSION AND GOALS During the course of our current ACISR and the work that it has facilitated over the past four years we achieved a number of important goals in optimizing clinical outcomes for individuals with eariy phase schizophrenia. At the same time, however, we have recognized that there are important gaps in the evidence necessary to make critical treatment decisions for young individuals experiencing psychotic signs and symptoms (which may or may not be an eariy manifestation of schizophrenia). Our work in ascertaining, recruiting and studying hundreds of first-episode schizophrenia and putafive prodromal schizophrenia patients over the years has highlighted the number of patients in whom the diagnosis remains unclear, and/or for whom treatment decisions are not sufficiently evidence based. Coupled with our belief that eariy, appropriate and consistent intervention is necessary to optimize outcomes in an early phase manifestation of a psychotic disorder in adolescents and young adults, we will systematically address a range of issues in this context. The 21 year old who presents with a psychosis associated with substance use, the 18 year old who presents with a mixture of attenuated positive and depressive symptoms, the 19 year old who presents with mania and psychotic symptoms are all individuals for whom antipsychotic medications might be considered, and are frequently used. At the same time that their use might be appropriate/efficacious in the short term, there are major unanswered questions regarding their intermediate and long-term use. What are the optimal treatments, dosing and duration of intervention to achieve remission, recovery, and to prevent relapse in such individuals? In addition, we also need to know how such patients are currently being evaluated and treated in the larger community in order to understand the "real worid" issues that confront patients and families as well as the mental health professionals working in those settings. In this context, we have also learned that therapeutic engagement and adherence with treatment are key drivers of outcomes in all of the populations that we have treated, and, will continue to be in the additional groups we will now study. These issues need to be addressed far more adequately and proactively in the community than they are currently. As we consider the appropriateness, acceptability and benefit-to-risk ratio of antipsychotic treatments in adolescents and young adults we also have to consider and address the potential effects of our interventions on global health and in particular those illness- and treatment-related factors which contribute so dramatically to increased medical morbidity and mortality in these populations (i.e. weight gain, metabolic syndrome, and smoking). This is a brief perspective on the background and rationale for our current proposal